Compounds including 2-amino-benzimidazole as a mother nucleus have an extensive value in application, which are very important intermediates of various drugs, weedicides, pesticides and the like, and also are primary pharmacophoric groups of a number of drug molecules, and thus they have wide spectrum drug effect.
In the field of medicine, due to the imidazole rings or heterocyclic benzimidazoles having certain pharmaceutical activities, such as anti-parasitic, anti-bacterial, anti-inflammatory, anticancer, sedative, and diuretic, the derivatives containing such functional structure have broad application prospects. For example, antineoplastic Denibulin, anthelmintic Mebendazole and Albendazole, antihistamine Emedastine, Astemizole, Norastemizole, Mizolastine etc.
The commonly used method for preparing 2-amino-benzimidazole derivatives is by means of the desulfuration and cyclization of 2-(2-aminoaryl) thiourea with disubstituted carbodiimide, however, highly toxic mercuric oxide, cuprous oxide, chlorine or methyl iodide are used in such method. Thus, many disadvantages exist in such method, such as, high cost, environmental pollution and complicated operation.
Another simple method for preparing 2-amino benzimidazole derivatives is to react the 2-chloro benzimidazole with aniline derivatives in the temperature of 140-150° C., but the yield is low and many by-products are generated in this method.
Such methods are as described in the following references: (1) J. Comb. Chem. 2006, 8, 907. (2) Synthesis 1977, 864-865. (3) Tetrahedron Lett. 2006, 47, 3747-3750. (4) Tetrahedron Lett. 1999, 40, 1103-1106. (5) Tetrahedron Lett. 2002, 43, 7303-7306. (6) Tetrahedron Lett. 2004, 45, 7167-7170. (7) Synthesis 1974, 41-42.